INDICATIONS and IMPORTANT SAFETY INFORMATION
INDICATIONS AND USAGE
Gadavist®(gadobutrol) injection is a gadolinium-based contrast agent indicated for use with magnetic resonance imaging (MRI):
- To detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system in adult and pediatric patients including term neonates.
- To assess the presence and extent of malignant breast disease in adult patients.
- To assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD).
Gadavist® is indicated for use in magnetic resonance angiography (MRA):
- To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients including term neonates.
EOVIST® (gadoxetate disodium) Injection
INDICATIONS AND USAGE
Eovist® is indicated for intravenous use in magnetic resonance imaging (MRI) of the liver to detect and characterize lesions in patients with known or suspected focal liver disease.
IMPORTANT SAFETY INFORMATION FOR GADAVIST® AND EOVIST®
Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs.
Contraindication and Important Information about Hypersensitivity Reactions: Gadavist® and Eovist® are contraindicated in patients with history of severe hypersensitivity reactions to the agent. Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory, or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following Gadavist® and Eovist® administration. Before administration, assess all patients for any history of a reaction to contrast media, bronchial asthma and/or allergic disorders. These patients may have an increased risk for a hypersensitivity reaction.
Gadolinium Retention: Gadolinium is retained for months or years in several organs. Linear GBCAs cause more retention than macrocyclic GBCAs. At equivalent doses, retention varies among the linear agents. Retention is lowest and similar among the macrocyclic GBCAs. Consequences of gadolinium retention in the brain have not been established, but they have been established in the skin and other organs in patients with impaired renal function. While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions. Consider the retention characteristics of the agent and minimize repetitive GBCA studies, when possible.
Acute Kidney Injury: In patients with chronic renal impairment, acute kidney injury sometimes requiring dialysis has been observed with the use of GBCAs. Do not exceed the recommended dose; the risk of acute kidney injury may increase with higher than recommended doses.
ADDITIONAL IMPORTANT SAFETY INFORMATION FOR GADAVIST®
Extravasation and Injection Site Reactions: Ensure catheter and venous patency before the injection of Gadavist®. Extravasation into tissues during Gadavist® administration may result in moderate irritation.
Overestimation of Extent of Malignant Disease in MRI of the Breast: Gadavist® MRI of the breast overestimated the histologically confirmed extent of malignancy in the diseased breast in up to 50% of the patients.
Low Sensitivity for Significant Arterial Stenosis: The performance of Gadavist® MRA for detecting arterial segments with significant stenosis (>50% renal, >70% supra-aortic) has not been shown to exceed 55%. Therefore, a negative MRA study alone should not be used to rule out significant stenosis.
Adverse Reactions: The most frequent (≥0.5%) adverse reactions associated with Gadavist® in clinical studies were headache (1.7%), nausea (1.2%) and dizziness (0.5%).
ADDITIONAL IMPORTANT SAFETY INFORMATION FOR EOVIST®
Extravasation and Injection Site Reactions: Ensure catheter and venous patency before the injection of Eovist®. Extravasation into tissues during Eovist® administration may result in local tissue reactions. Strictly avoid intramuscular administration of Eovist® because it may cause myocyte necrosis and inflammation.
Interference with Laboratory Tests: Serum iron determination using complexometric methods may result in falsely high or low values for up to 24 hours after the examination with Eovist®.
Interference with Visualization of Liver Lesions: End-stage renal failure or hepatic failure may impair Eovist® imaging performance. In patients with elevated serum ferritin or serum bilirubin >3 mg/dL, reduced hepatic contrast was observed.
Adverse Reactions: The most frequent (≥0.5%) adverse reactions associated with Eovist® are nausea (1.1%), headache (1.1%), feeling hot (0.8%), dizziness (0.6%), and back pain (0.6%).
ULTRAVIST® (iopromide) injection
INDICATIONS AND USAGE
Ultravist® (iopromide) injection is an iodinated contrast agent indicated for:
Intra‐arterial Procedures*: 300 mg Iodine per mL for cerebral arteriography and peripheral arteriography; 370 mg Iodine per mL for coronary arteriography and left ventriculography, visceral angiography, and aortography.
Intravenous Procedures*: 300 mg Iodine per mL for excretory urography; 300 mg Iodine per mL and 370 mg Iodine per mL for contrast Computed Tomography (CT) of the head and body (intrathoracic, intraabdominal and retroperitoneal regions) for the evaluation of neoplastic and non‐neoplastic lesions. The usefulness of contrast enhancement for the investigation of the retrobulbar space and of low grade or infiltrative glioma has not been demonstrated.
*For information on the concentrations and doses for the Pediatric Population [see Dosage and Administration (2.3) and Use in Specific Populations (8.4) in the Full Prescribing Information].
IMPORTANT SAFETY INFORMATION
Inadvertent intrathecal administration may cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema.
Contraindications: Ultravist® injection is contraindicated for intrathecal use.
Preparatory dehydration (for example, prolonged fasting and the administration of a laxative before Ultravist® injection) is contraindicated in pediatric patients because of risk of renal failure.
Anaphylactoid Reactions: Life‐threatening or fatal anaphylactoid reactions may occur during or after Ultravist® administration, particularly in patients with allergic disorders. Increased risk is associated with a history of previous reaction to a contrast agent, a known sensitivity to iodine and known allergic disorders or other hypersensitivities. Exercise extreme caution when considering the use of iodinated contrast agents in patients with these histories or disorders. Emergency facilities and personnel trained in the treatment of anaphylactoid reactions should be available for at least 30 to 60 minutes after Ultravist® administration.
Contrast Induced Acute Kidney Injury: Acute kidney injury, including renal failure, may occur after intravascular administration of Ultravist®. Risk factors include: pre‐existing renal insuﬃciency, dehydration, diabetes mellitus, congestive heart failure, advanced vascular disease, elderly age, concomitant use of nephrotoxic or diuretic medications, multiple myeloma/paraproteinemia, repetitive and/or large doses of Ultravist®. Use the lowest necessary dose of Ultravist® in patients with renal impairment. Hydrate patients, as appropriate, prior to and following Ultravist® administration.
Cardiovascular Reactions: Hemodynamic disturbances including shock and cardiac arrest may occur during or shortly after administration of Ultravist®. Observe patients with preexisting cardiovascular disease for several hours following Ultravist® administration.
Thromboembolic Complications: Angiography may be associated with local and distal organ damage, ischemia, thromboembolism and organ failure. In angiographic procedures, consider the possibility of dislodging plaques or damaging or perforating the vessel wall. The physicochemical properties of the contrast agent, the dose and the speed of injection can inﬂuence the reactions. Monitor electrocardiograms and vital signs throughout the procedure. Exercise care when performing venography in patients with suspected thrombosis, phlebitis, severe ischemic disease, local infection, venous thrombosis or a totally obstructed venous system. Clotting may occur when blood remains in contact with syringes containing iodinated contrast agents. Avoid angiography whenever possible in patients with homocystinuria because of the risk of inducing thrombosis and embolism.
Reactions in Patients with Hyperthyroidism, Pheochromocytoma, or Sickle Cell Disease: Thyroid storm has occurred after the intravascular use of iodinated contrast agents in patients with hyperthyroidism, or with autonomously functioning thyroid nodule. Evaluate the risk in such patients before use of any iodinated contrast agent. Administer iodinated contrast agents with extreme caution in patients with known or suspected pheochromocytoma. Inject the minimal amount of contrast necessary. Contrast agents may promote sickling in individuals who are homozygous for sickle cell disease when administered intravascularly.
Extravasation: Extravasation of Ultravist® may cause tissue necrosis and/or compartment syndrome, particularly in patients with severe arterial or venous disease.
Increased Radiation Exposure: The decision to use contrast enhancement is associated with risk and increased radiation exposure.
Interference with Image Interpretation: The use of Ultravist® injection may obscure some lesions which were seen on non-contrast CT scans. Calciﬁed lesions are less likely to enhance. The enhancement of tumors after therapy may decrease. The opaciﬁcation of the inferior vermis following contrast agent administration has resulted in false-positive diagnosis. Cerebral infarctions of recent onset may be better visualized with contrast enhancement. However, older infarctions may be obscured by the contrast agent. In patients with normal blood-brain barriers and renal failure, iodinated contrast agents have been associated with blood-brain barrier disruption and accumulation of contrast in the brain. Accumulation of contrast in the brain also occurs in patients where the blood-brain barrier is known or suspected to be disrupted.
Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering Ultravist® to patients with a history of a severe cutaneous adverse reaction to Ultravist®.
Most Common Adverse Reactions: Most common adverse reactions (>1%) are headache, nausea, injection site and infusion site reactions, vasodilatation, vomiting, back pain, urinary urgency, chest pain, pain, dysgeusia, and abnormal vision.